Endothelin‐1 signalling controls early embryonic heart rate in vitro and in vivo. (11th December 2013)

• Record Type: Journal Article
• Authors: Karppinen, S.; Rapila, R.; Mäkikallio, K.; Hänninen, S. L.; Rysä, J.; Vuolteenaho, O.; Tavi, P.
• Is Part Of: Acta physiologica. Volume 210:Number 2(2014:Feb.)
• Page Start: 369
• Page End: 380
• Publication Date: 2013-12-11
• Subjects: Physiology -- Periodicals; Physiology -- Research -- Periodicals; 612
• DOI: 10.1111/apha.12194
• Languages: English
• ISSNs: 1748-1708

Abstract

<abstract abstract-type="main" id="apha12194-abs-0001"> <title>Abstract</title> <sec id="apha12194-sec-0001" sec-type="section"> <title>Aim</title> <p>Spontaneous activity of embryonic cardiomyocytes originates from sarcoplasmic reticulum (SR) Ca<sup>2+</sup> release during early cardiogenesis. However, the regulation of heart rate during embryonic development is still not clear. The aim of this study was to determine how endothelin‐1 (ET‐1) affects the heart rate of embryonic mice, as well as the pathway through which it exerts its effects.</p> </sec> <sec id="apha12194-sec-0002" sec-type="section"> <title>Methods</title> <p>The effects of ET‐1 and ET‐1 receptor inhibition on cardiac contraction were studied using confocal Ca<sup>2+</sup> imaging of isolated mouse embryonic ventricular cardiomyocytes and ultrasonographic examination of embryonic cardiac contractions <italic>in utero</italic>. In addition, the amount of ET‐1 peptide and ET receptor a (ETa) and b (ETb) mRNA levels were measured during different stages of development of the cardiac muscle.</p> </sec> <sec id="apha12194-sec-0003" sec-type="section"> <title>Results</title> <p>High ET‐1 concentration and expression of both ETa and ETb receptors was observed in early cardiac tissue. ET‐1 was found to increase the frequency of spontaneous Ca<sup>2+</sup> oscillations in E10.5 embryonic cardiomyocytes <italic>in vitro</italic>. Non‐specific inhibition of ET receptors with tezosentan caused arrhythmia and bradycardia in isolated embryonic cardiomyocytes and in whole embryonic hearts both <italic>in vitro</italic> (E10.5) and <italic>in utero</italic> (E12.5). ET‐1‐mediated stimulation of early heart rate was found to occur via ETb receptors and subsequent inositol trisphosphate receptor activation and increased SR Ca<sup>2+</sup> leak.</p> </sec> <sec id="apha12194-sec-0004" sec-type="section"> <title>Conclusion</title> <p>Endothelin‐1 is required to maintain a sufficient heart rate, as well as to prevent arrhythmia during early development of the mouse heart. This is achieved through ETb receptor, which stimulates Ca<sup>2+</sup> leak through IP<sub>3</sub> receptors.</p> </sec> </abstract>